To assess the frequency of complex V defects, a team of French researchers including researchers from the Institute of Myology systematically sequenced the MT-ATP6 / 8 genes in 512 consecutive patients. They performed functional analysis in muscle or fibroblasts for 12 of the 27 putative homoplasmic mutations and in cybrids for 4 of them. Fibroblasts, muscles and cybrids with known deleterious mutations were tested in parallel: spectrophotometric tests for oxidative phosphorylation, western blots, structural analysis, ATP production, glycolysis and evaluation of cell proliferation.
The researchers demonstrated the deleterious nature of three original mutations. A striking gradation in the severity of the consequences of mutations and differences between muscle, fibroblasts and cybrids implied a likely underdiagnosis of human V complex defects.
